Despite advances in understanding the underlying genetics, squamous cell carcinoma of the head and neck (SCCHN) remains a major health risk and one of the leading causes of mortality in the world. Current standards of treatment have significantly improved long-term survival rates of patients, but second tumors and metastases still remain the most frequent cause of high mortality in SCCHN patients. A better understanding of the underlying genetic mechanisms of SCCHN tumorigenesis will help in developing better diagnostics and, hence, better cures. In this article we will briefly outline the current state of diagnostics and treatment and our understanding of the molecular causes of SCCHN.